Could Pig Organs Save Human Lives?
Quick Summary
- The demand for donor organs has vastly outpaced supply for decades, and no amount of public awareness campaigns has been capable of closing this gap.
- Xenotransplantation is the transplantation of organs from one species into another and has been an enticing idea since the early twentieth century.
- Of all the animals considered for xenotransplantation, pigs have emerged as the leading candidates.
Every day, seventeen people in the United States die waiting for an organ transplant while more than 100,000 patients are currently on national waiting lists, and kidneys being the most critically short supply. The demand for donor organs has vastly outpaced supply for decades, and no amount of public awareness campaigns has been capable of closing this gap. However, a very different solution is emerging from research labs. This technology instead involves pigs, molecular scissors, and reimagining where transplantable organs come from.
Xenotransplantation is the transplantation of organs from one species into another and has been an enticing idea since the early twentieth century. For most of its history, the immune system faced complications in accepting the logistics of a new organ. When the human body encountered pig tissue, it recognized the foreign sugars and proteins on the cell surface and launched an immediate rejection response.
Of all the animals considered for xenotransplantation, pigs have emerged as the leading candidates. Porcine organs are anatomically close to human organs in size and physiology. They are also easy to breed, reach maturity quickly, and can be raised in controlled environments. Compared to non-human primates, pigs have fewer ethical concerns and dramatically lower zoonotic disease risk when properly screened.
However, there are major challenges in terms of pathobiological barriers such as overcoming immune incompatibility. In fact, there are several different types of immune rejections that can occur after a transplant surgery. Two of the more common forms are Hyperacute Rejection, which occurs minutes to hours after xenotransplantation and Acute Humoral Xenograft Rejection, which occurs days to weeks after. Some classes of molecular markers on pig cells that trigger the human immune system include alpha-Gal sugars, Neu5Gc glycans , and Sd(a) antigens. These markers often alert human antibodies catalyzing the attack. Currently, nearly forty different gene edits have been conducted in the hopes of reducing these effects and avoiding triggering human immune response. This ability to genetically engineer pig organs is a large improvement towards future clinical applications.
One of the more common genetic engineering tools includes CRISPR (Clustered regularly interspaced short palindromic repeats). It works by recognizing and hydrolyzing pathogen genetic material through an RNA component and protein (Cas nuclease). It operates by The usage of CRISPR-Cas9 has successfully disengaged harmful molecular markers. By directing the Cas9 protein to precise genomic locations using guide RNA, researchers knock out pig genes that cause human immune rejection and also insert human genes to improve compatibility. A more revolutionary idea involves deactivating porcine endogenous retroviruses or PERVs that are viral sequences embedded in the pig genome that could potentially infect human cells.
Similarly, the eGenesis group engineered a porcine donor carrying 69 genomic edits: knockout of all three glycan antigen genes, insertion of seven human transgenes (including CD46, CD55, THBD, and CD47) to regulate, coagulation, and innate immunity, and full PERV inactivation. When these kidneys were transplanted into cynomolgus monkeys, the recipients survived up to two years, which became a major record at its time.
In recent years, a small but growing number of patients have successfully received such transplants. In January of last year, the Massachusetts General Hospital performed the completion of their second pig-to-human kidney transplant. While in 2024, they were the first hospital to transplant a genetically-edited pig kidney into a living human. These procedures followed a cardiac xenotransplant in 2022 at the University of Maryland, where surgeons placed a 10-gene-edited pig heart into a patient with end-stage heart failure
In the last few decades, the use of the CRISPR/Cas system in genetic engineering has majorly contributed to the development of Xenotransplantation technology, especially in improving immunosuppression protocols, which has been reflected in organ survival. In comparison to current human transplantation, the success in xenotransplantation will open the door of relief for a number of patients currently on the waiting list for transplantations.
Sources:
https://www.mdpi.com/1422-0067/22/6/3196
https://pmc.ncbi.nlm.nih.gov/articles/PMC12391572/
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1735113/full
https://www.frontiersin.org/journals/transplantation/articles/10.3389/frtra.2025.1559512/full